This research program is designed (1) to attempt to answer the question as to which elements of the carotid body are the initial transducing receptor sensors--the glomus cells themselves or the sensory nerve terminals; (2) to study the location and learn the role of neurotransmitter or neuromodulator substances in initiating a nerve impulse from glomus cell to sensory nerve terminal or vice versa; and (3) to contribute infomration about the details of the innervation of the carotid body. Investigations will involve the possible occurrence of adenosine in the carotid body, carotid sinus nerve, petrosal ganglion, and central portions of the ganlion cells and their terminations in the nucleus solitarius. Studies will be performed on the cellular site of origin and termination of substance P fibers found inthe carotid body. The occurrence and localization of enkephalin will be investigated to determine if it is present in all glomus cells and if it exists vesicularly or extra-vesicularly. Also it will be determined if the effects of various substances which cause alteration or depletion of dopamine have concomittant effects ont he content of enkephalin. Experimental studies will be performed on the nerve fiber size and content of the carotid sinus nerve and investigations performed to study the degeneration of these fibers after various experimental procedures to determine their cellular origin. It will be attempted to see if any efferent fibers arise from neurons in the brain or if the sympathetic ganglia contribute fibers to the sinus nerve or if it is a purely sensory nerve. Some morphological and physiological effects of increased activity induced by hypoxia on the carotid body will be studied. Glucose metabolism will be studied in the normal and denervated carotid body during increased activity (hypoxia). Also effects of hypoxia on the disposition of dense-cored vesicles, especially those with calcium-binding sites on the vesicular limiting membrane, will be studied in normal and denervated carotid bodies. The effects of hypoxia on the uptake of systemically administered horeradish peroxidase by normal and denervated carotid bodies will also be investigated. These latter studies should provide crucial evidence for determining whether glomus cells or nerve terminals are the sensory tansducers. Sudden changes in respiratory response (apnea) or the onset of illnesses at high altitudes might well be related to a malfunctioning of the carotid body due to disturbance of tis innervation and/or content of transmitter substances, resulting in a deficit of respiratory response.